Osamu Shiono

Predictive and Prognostic Value of Metabolic Tumor Volume (MTV) in Patients with Laryngeal Carcinoma Treated by Radiotherapy (RT) / Concurrent Chemoradiotherapy (CCRT)

Purpose To evaluate the predictive and prognostic value of pretreatment metabolic tumor volume (MTV) in patients with treated by radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). Methods We reviewed the records of 118 patients with newly diagnosed laryngeal carcinoma, who had been treated by RT or CCRT. Pretreatment positron emission tomography (PET) was performed, and MTV values were obtained by contouring margins of standardized uptake value. Clinical factors and MTV were analyzed for their association with survival. Results Patients with residual disease showed a significantly higher MTV than those with a complete response (CR) after primary treatment. Univariate analysis showed that the patients with a high MTV had a significantly lower disease-free survival (DFS) (p < 0.001). Subsite (p = 0.010), T-stage (p < 0.001), nodal metastasis (p < 0.001) and clinical stage (p < 0.001) also correlated significantly with DFS. In the multivariate analysis, MTV and clinical stage were both found to be independent prognostic factors for DFS (p = 0.001, p = 0.034, respectively). The 3-year DFS for patients with a high MTV were significantly poorer than those with a low MTV (p < 0.001). Conclusions MTV of the primary tumor is a significant prognostic factor for DFS in patients with laryngeal carcinoma treated by RT or CCRT. The results imply that MTV could be an important factor when planning treatment and follow-up for patients with laryngeal carcinoma.

Treatment results and prognostic factors for advanced squamous cell carcinoma of the head and neck treated with salvage surgery after concurrent chemoradiotherapy

BackgroundFor primary organ preservation, concurrent chemoradiotherapy (CCRT) is performed for advanced squamous cell carcinoma of the head and neck (SCCHN). In this organ-preservation setting with CCRT, surgery is reserved as a salvage treatment in cases of locoregional failure after CCRT. The purpose of the study was to review our experience with salvage surgery after CCRT for patients with SCCHN and to evaluate the effectiveness and prognostic factors affecting survival.MethodsThe records of patients with stage II-IVB SCC of the larynx, oropharynx, or hypopharynx treated with salvage surgery after CCRT between 1998 and 2012 were reviewed.ResultsA total of 645 patients with previously untreated, resectable SCC of the larynx, oropharynx, or hypopharynx received CCRT. Salvage surgery was performed for 78 of 225 patients with residual or recurrent tumors. The 5-year overall survival (OS) and disease-specific survival rates for patients who received salvage surgery were 61.0 and 65.5xa0%, respectively. Stage IV, poorly differentiated, synchronous double cancer, and surgical complications were significant predictors of unfavorable OS on multivariate analysis. Postoperative complications were observed in 30 patients (38.5xa0%).ConclusionsSalvage surgery is the best therapeutic option for failure after CCRT for SCCHN because of its good survival rate, although a high surgical complication rate is seen. Patients with initial stage IV tumors, poorly differentiated SCC, or synchronous double cancer are considered for further adjuvant treatment.

Imaging strategy for response evaluation to chemoradiotherapy of the nodal disease in patients with head and neck squamous cell carcinoma

BackgroundDefinitive chemoradiotherapy (CRT) is used to treat lymph node metastatic head and neck cancer patients. Regional control of the neck disease is important to improve the prognosis, and the accuracy of the method used to evaluate the metastatic lymph node(s) after CRT is crucial to the decision-making process for any following salvage surgery.MethodsPatients undergoing CRT were divided in two groups of patients of those showing complete clinical response (CR) and those showing clinical non-response (non-CR), as assessed by computed tomography (CT) and/or magnetic resonance imaging (MRI), ultrasonography, fluorodeoxyglucose-positron emission tomography (FDG-PET), and fine needle aspiration cytology. The responses (CR vs. non-CR) were compared with the actual clinical outcomes. For the interim analysis, the study period was broken down into two periods, namely, the exploratory phase (patients treated between January 2002 and April 2012) and the validating phase (patients treated between May 2012 and January 2014).ResultsThe sensitivity, specificity, and accuracy were as follows: CT and/or MRI, 66.7, 73.8, and 72.8xa0%, respectively, in the exploratory phase; ultrasonography, 91.7, 70.6, and 73.4xa0%, respectively, in the exploratory phase and 80.0, 82.8, and 82.4xa0%, respectively, in the validating phase; FDG-PET, 50.0, 97.5, and 91.3xa0%, respectively, in the exploratory phase and 60.0, 100, and 94.1xa0%, respectively, in the validating phase; cytology, 68.4, 95.9, and 90.3xa0%, respectively, in the exploratory phase and 66.7, 100, and 85.7xa0%, respectively, in the validating phase.ConclusionsBased on our results, CT and/or MRI appear to be inadequate methods for the evaluation of the response of lymph node(s) to CRT. In contrast, ultrasonography appears to be a highly sensitive and useful tool for positive screening at 6–8xa0weeks after CRT, and FDG-PET appears to be a highly specific and useful tool for negative screening at 8–12xa0weeks after CRT.

Differential expression of periostin in the nasal polyp may represent distinct histological features of chronic rhinosinusitis

OBJECTIVEnChronic rhinosinusitis (CRS) is thought to be a multifactorial disease, and it is classified into a number of subtypes according to clinicohistological features. Periostin, a 90-kDa secreted protein, was reported to exist in nasal polyps (NPs) associated with CRS. We compared the expression of periostin with the degree of eosinophilic infiltration as well as tissue remodeling.nnnMATERIALS AND METHODSnTissue samples were collected from 28 patients of CRS with NPs, and clinicohistological features were evaluated. The pattern of periostin expression was assessed immunohistochemically.nnnRESULTnTwo patterns of periostin expression was observed in nasal polyps: diffuse type, in which periostin was expressed throughout the lamina propria starting just below the basement membrane, and superficial type, in which the protein was detected only in the subepithelial layers between the basement membrane and the nasal gland. The average infiltrated eosinophil count in the diffuse type was significantly higher than that in the superficial type (diffuse type 360.5±393.0 vs. superficial type 8.46±13.81, p=0.001). Tissue remodeling was observed in 17 (85.0%) of the 20 diffuse-type nasal polyps, but only in one (12.5%) of the eight superficial-type nasal polyps (p<0.001).nnnCONCLUSIONnAt least two distinct patterns of periostin expression were observed in the nasal polyps associated with CRS in accordance with the heterogeneous mechanisms underlying the pathogenesis of CRS with NPs.

Phase II trial of concurrent bio-chemoradiotherapy using docetaxel, cisplatin, and cetuximab for locally advanced head and neck squamous cell carcinoma

PurposeAlthough locally advanced head and neck squamous cell carcinoma (HNSCC) can be effectively treated using chemoradiotherapy (CRT) with docetaxel (DTX), and cisplatin (CDDP) plus 5-fluorouracil (TPF-CRT), severe adverse events (especially neutropenia) can limit treatment adherence. Therefore, we evaluated the safety and efficacy of a new chemotherapy regimen that consisted of DTX and CDDP plus cetuximab (Cmab) with concurrent radiotherapy.MethodsBio-chemoradiotherapy (B-CRT) using DTX, CDDP, and Cmab was administrated to patients with locally advanced HNSCC, and its safety and efficacy were evaluated.ResultsInterim analysis of nine patients revealed severe neutropenia in five patients (56xa0%) and leukopenia in seven patients (78xa0%); hence, the study was terminated. One patient experienced disease-free survival using only B-CRT.ConclusionsNeutropenia was equally severe for B-CRT, compared to TPF-CRT. Based on the limited sample size, it is impossible to conclude that B-CRT has non-inferior efficacy, compared to TPF-CRT.

Predictive markers, including total lesion glycolysis, for the response of lymph node(s) metastasis from head and neck squamous cell carcinoma treated by chemoradiotherapy

BackgroundChemoradiotherapy (CRT) is used to treat cervical lymph node(s) metastatic head and neck cancer patients. Evaluation and treatment of lymph node(s) after CRT is important to improve the prognosis.MethodsPrior to CRT, we determined the TNM stage by visual and imaging examinations. Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated from the results of fluorodeoxyglucose-positron emission tomography (FDG-PET). After CRT, the patients were divided in two groups—complete response (CR) and non-CR—and their responses were compared with the clinical characteristics.ResultsT4, N2b, N2c and TLG2.5xa0≥18.8 were statistically significant predictive indices before CRT. The odds ratio, 95xa0% confidence interval and p value were, respectively—T4: 2.73, 1.15–6.51, 0.0230; N2b: 6.96, 1.50–32.3, 0.0132; N2c: 11.80, 2.37–58.50, 0.00258; and TLG2.5xa0≥18.8: 6.25, 2.17–18.00, 0.000672.ConclusionsTLG was found to be a good predictive factor for metastatic lymph node(s) prior to CRT treatment. After CRT treatment, FDG-PET was found to be highly specific and useful for negative screening.

Prognostic significance of metabolic tumor volume in patients with piriform sinus carcinoma treated by radiotherapy with or without concurrent chemotherapy

The purpose of this study was to elucidate the prognostic significance of the pretreatment metabolic tumor volume (MTV) in patients with piriform sinus carcinoma treated by radiation‐based therapy.

Phase II study of concurrent chemoradiotherapy with S-1 in patients with stage II (T2N0M0) squamous cell carcinoma of the Pharynx or Larynx.

OBJECTIVEnThe goals of treatment for head and neck cancer are cure and organ-function preservation. For organ preservation, primary treatment via radiotherapy alone is thought to be insufficient for Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx. The objective of the present study was to investigate the efficacy and safety of concurrent chemoradiotherapy with S-1 for patients with Stage II squamous cell carcinoma of the pharynx or larynx for primary organ preservation.nnnMETHODSnPreviously untreated patients with Stage II squamous cell carcinoma of the larynx, oropharynx or hypopharynx received three courses of S-1 (40 or 50 mg twice a day; 2 weeks of administration followed by 1 week of rest every 3 weeks) during conventional radiotherapy (a single daily fraction of 1.8 Gy) to a total dose of 70.2 Gy. The primary endpoint was the local control rate at 3 years.nnnRESULTSnFrom August 2009 to October 2012, 37 patients were evaluated for the study. The overall response rate was 100%. The 3-year local control rate was 89.0% (95% confidence interval, 78.9-99.2%), and the 3-year overall survival rate was 97.2% (95% confidence interval, 91.8-100%). Mucositis and dermatitis in the radiation field were the most common acute adverse events observed. The rates of Grade 3 mucositis and dermatitis were 27 and 35%, respectively. No patients experienced Grade 4 acute adverse events. The treatment completion rate was 89.2%.nnnCONCLUSIONnConcurrent chemoradiotherapy with S-1 was safe and effective in improving local control for Stage II squamous cell carcinoma of the pharynx or larynx.

Surgery-based versus radiation-based treatment strategy for a high metabolic volume laryngeal cancer

We previously reported that the metabolic tumor volume (MTV) of a primary tumor was an independent prognostic factor for survival in laryngeal carcinoma treated by radiotherapy (RT)‐based protocol. The purpose of this study was to evaluate the difference in survival outcomes between surgery‐based and RT‐based treatment in patients with a MTV laryngeal cancer.

Efficacy and safety of postoperative bio-chemoradiotherapy using cetuximab and docetaxel for high-risk head and neck cancer patients in Japan

PurposeTo confirm the efficacy and safety of cetuximab and docetaxel in postoperative radiotherapy for high-risk head and neck cancer patients who cannot to be administered high-dose cisplatin.Patients and methodsThe eligibility criteria required stage III–IVB head and neck cancer patients who had undergone total resection, and for whom pathological evaluation revealed positive or close margins in the primary site and/or extracapsular nodal extension and/or two or more nodal metastases. In each case, the patients general condition prevented the use of high-dose cisplatin. Instead, they received cetuximab and docetaxel every week during a 66.6xa0Gy course of postoperative radiotherapy.ResultsEleven patients were enrolled; the median follow-up period was 22xa0months, and the 1- and 2-year disease free survival rates were 91 and 55%, respectively. Grade 3 adverse events included oral mucositis, radiation dermatitis, reduced white blood cell and neutrophil counts, lung infection, aspiration, and hyponatremia; however, no grade 4 adverse events were observed.ConclusionAdministration of cetuximab and docetaxel during postoperative radiotherapy for high-risk poor condition head and neck cancer patients in poor general condition was both feasible and tolerable. With the safety of this treatment confirmed, we propose a phase trail to further clarify the efficacy of cetuximab and docetaxel use for high-risk cisplatin-intolerant patients.